Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of α-syntrophin
Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of α-syntrophin
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DOI：
10.1038/sj.emboj.7600858
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发表时间：
2005-12-07
期刊：
影响因子：
11.4
通讯作者：
Zhang, MJ
中科院分区：
文献类型：
--
作者：
Yan, J;Wen, WY;Zhang, MJ
普列克底物蛋白同源结构域在细胞骨架动力学和信号转导中起着不同的作用。分裂PH结构域代表了PH结构域的一个独特亚类，其与许多蛋白质中“隐藏”的互补部分PH结构域相互作用。部分PH结构域是否单独作为独立的结构单元存在以及分裂的PH结构域的两半是否可以折叠在一起以形成完整的PH结构域尚不清楚。在这里，我们解决了α（-）syntrophin的PHN-PDZ-PHC串联的结构。α-促突触蛋白的分裂PH结构域采用典型的PH结构域折叠。α-突触营养蛋白的分离的部分PH结构域，尽管完全未折叠，但仍可溶于溶液中。两个分离的结构域的混合诱导从头折叠并产生稳定的PH结构域。我们的研究结果表明，两个互补的部分PH结构域能够相互结合，形成一个完整的PH结构域。我们进一步表明，PHN-PDZ-PHC串联形成了一个功能独特的超模块，其中分裂的PH结构域和PDZ结构域的功能协同结合肌醇磷脂。
Pleckstrin homology (PH) domains play diverse roles in cytoskeletal dynamics and signal transduction. Split PH domains represent a unique subclass of PH domains that have been implicated in interactions with complementary partial PH domains `hidden' in many proteins. Whether partial PH domains exist as independent structural units alone and whether two halves of a split PH domain can fold together to form an intact PH domain are not known. Here, we solved the structure of the PHN-PDZ-PHC tandem of alpha(-)syntrophin. The split PH domain of alpha-syntrophin adopts a canonical PH domain fold. The isolated partial PH domains of alpha-syntrophin, although completely unfolded, remain soluble in solution. Mixing of the two isolated domains induces de novo folding and yields a stable PH domain. Our results demonstrate that two complementary partial PH domains are capable of binding to each other to form an intact PH domain. We further showed that the PHN-PDZ-PHC tandem forms a functionally distinct supramodule, in which the split PH domain and the PDZ domain function synergistically in binding to inositol phospholipids.